A Study of Calderasib (MK-1084) Plus Pembrolizumab (MK-3475) in Participants With KRAS G12C Mutant Non-small Cell Lung Cancer (NSCLC) With Programmed Cell Death Ligand 1 (PD-L1) Tumor Proportion Score (TPS) ≥50% (MK-1084-004/KANDLELIT-004)

Purpose

This is a study evaluating the efficacy and safety of calderasib with pembrolizumab as first-line treatment in participants with locally advanced or metastatic non-small cell lung cancer (NSCLC) with identified Kirsten rat sarcoma viral oncogene homolog G12C (KRAS G12C) mutation and programmed cell death ligand 1 (PD-L1) tumor proportion score (TPS) ≥50%. There are two primary study hypotheses: Hypothesis 1: Combination of calderasib and pembrolizumab is superior to placebo plus pembrolizumab with respect to progression free survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by blinded independent central review (BICR). Hypothesis 2: Combination of calderasib plus pembrolizumab is superior to placebo plus pembrolizumab with respect to overall survival (OS).

Condition

  • Non-small Cell Lung Cancer

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Has histologically or cytologically confirmed diagnosis of non-small cell lung cancer (NSCLC) - Has newly diagnosed Stage IIIB/IIIC NSCLC, not eligible for curative resection or curative chemotherapy/radiation as determined by a multidisciplinary tumor board and/or by radiation oncologist, surgeon, and medical oncologist or Stage IV (M1a, M1b, or M1c) by American Joint Committee on Cancer (AJCC) Staging Manual, Version 8 - Provides an archival tumor tissue sample (≤5 years) or newly obtained core, incisional, or excisional biopsy of a tumor lesion not previously irradiated to enable central laboratory testing of kirsten rat sarcoma (KRAS) G12C mutation status, PD-L1 status, and biomarker research - If have had adverse events (AEs) due to previous anticancer therapies, must have recovered to < Grade 1 or baseline - If human immunodeficiency virus (HIV)-infected, must have well controlled HIV on antiretroviral therapy (ART) - If Hepatitis B surface antigen (HBsAg) positive, have received Hepatitis B Virus (HBV) antiviral therapy for at least 4 weeks, and have undetectable HBV viral load - If a participant has a history of Hepatitis C virus (HCV) infection, HCV viral load is undetectable

Exclusion Criteria

  • Has diagnosis of small cell lung cancer. For mixed tumors, if small cell elements are present, the participant is ineligible - Has active inflammatory bowel disease requiring immunosuppressive medication or previous clear history of inflammatory bowel disease - Has known history of, or active, neurologic paraneoplastic syndrome - Has an active infection requiring systemic therapy, with exceptions - Has uncontrolled, significant cardiovascular disease or cerebrovascular disease - Has one or more of the following ophthalmological findings/conditions: intraocular pressure >21 mmHg and/or any diagnosis of glaucoma, diagnosis of central serous retinopathy, retinal vein occlusion, or retinal artery occlusion, diagnosis of retinal degenerative disease - Has received prior systemic anticancer therapy for their locally advanced or metastatic NSCLC - Has received radiation therapy to the lung that is >30 Gray within 6 months of start of study intervention - Has received radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not required corticosteroids, and not have had radiation pneumonitis - Has known active central nervous system metastases and/or carcinomatous meningitis - Known additional malignancy that is progressing or has required active treatment within the past 3 years - Has active autoimmune disease that has required systemic treatment in the past 2 years - Has history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease - Is HIV-infected and has a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease - Has history of allogenic tissue/solid organ transplant - Has not fully recovered from any effects of major surgical procedure

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Triple (Participant, Investigator, Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Calderasib with Pembrolizumab 		Participants receive pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to 35 cycles and calderasib by oral tablets until discontinuation criterion is met.
  • Drug: Calderasib
    Oral tablets
    Other names:
    • MK-1084
  • Biological: Pembrolizumab
    IV infusion
    Other names:
    • MK-3475
    • KEYTRUDA ®
Active Comparator
Placebo with Pembrolizumab 		Participants receive pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to 35 cycles and placebo by oral tablets once daily until discontinuation criterion is met.
  • Other: Placebo
    Oral tablets
  • Biological: Pembrolizumab
    IV infusion
    Other names:
    • MK-3475
    • KEYTRUDA ®

Recruiting Locations

CBCC Global Research, Inc. ( Site 0123)
Bakersfield, California 93309
Contact:
Study Coordinator
661-322-2206

Beverly Hills Cancer Center ( Site 0116)
Beverly Hills, California 90211
Contact:
Study Coordinator
310-432-8955

Stamford Hospital ( Site 0136)
Stamford, Connecticut 06902
Contact:
Study Coordinator
877-233-9355

Mount Sinai Cancer Center ( Site 0137)
Miami Beach, Florida 33140
Contact:
Study Coordinator
305-674-2625

Orchard Healthcare Research Inc. ( Site 0115)
Skokie, Illinois 60077
Contact:
Study Coordinator
224-534-7580

Truman Medical Center ( Site 0126)
Kansas City, Missouri 64108
Contact:
Study Coordinator
816-404-4093

Cox Medical Center North ( Site 0133)
Springfield, Missouri 65807
Contact:
Study Coordinator
417-875-3000

St. Vincent Frontier Cancer Center-Research ( Site 0105)
Billings, Montana 59102
Contact:
Study Coordinator
402-238-6685

Atlantic Health System Morristown Medical Center ( Site 0121)
Morristown, New Jersey 07960
Contact:
Study Coordinator
973-275-7788

New York Oncology Hematology, P.C. ( Site 0132)
Albany, New York 12206
Contact:
Study Coordinator
518-489-3612

University of Cincinnati Medical Center-University of Cincinnati Cancer Center ( Site 0103)
Cincinnati, Ohio 45219
Contact:
Study Coordinator
513-556-6000

Lancaster General Hospital - Ann B Barshinger Cancer Institute ( Site 0134)
Lancaster, Pennsylvania 17601
Contact:
Study Coordinator
717-544-9400

Oncology Consultants P.A. ( Site 0113)
Houston, Texas 77030
Contact:
Study Coordinator
713-600-0900

Circuit Clinical/SSM Health Dean Medical Group ( Site 0129)
Madison, Wisconsin 53715
Contact:
Study Coordinator
608-410-2767

More Details

Status
Recruiting
Sponsor
Merck Sharp & Dohme LLC

Study Contact

Toll Free Number
1-888-577-8839
Trialsites@msd.com